Recombinase Polymerase Amplification Assay for Rapid Diagnostics of Dengue Infection

PLoS One. 2015 Jun 15;10(6):e0129682. doi: 10.1371/journal.pone.0129682. eCollection 2015.

Abstract

Background: Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF). Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV). Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA) assays were developed to detect DENV1-4.

Methodology/principal findings: Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand). In Kedougou, the RT-RPA was operated at an ambient temperature of 38 °C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively.

Conclusions/significance: During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dengue / diagnosis*
  • Dengue / virology*
  • Dengue Virus / classification
  • Dengue Virus / genetics*
  • Humans
  • Nucleic Acid Amplification Techniques / methods*
  • RNA, Viral / genetics
  • Reproducibility of Results
  • Senegal
  • Sensitivity and Specificity
  • Thailand

Substances

  • RNA, Viral

Grants and funding

This study was funded by a grant from the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) contract no: VN 811-40270. http://www.giz.de. The Bangkok cohort study was funded by the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative, and European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement number 282 378. http://cordis.europa.eu/fp7/health/. The funders had no role in design of the study, data collection and analysis, decision to publish, or preparation of the manuscript.